search
Back to results

A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Transplantation

Primary Purpose

Multiple Myeloma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Granix
High dose melphalan (HDR)
Autologous Stem Cell Transplant (ASCT)
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Symptomatic multiple myeloma requiring treatment
  • Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy
  • At least 18 years of age
  • Adequate autologous stem cell collection, defined as an unmanipulated, cryopreserved, peripheral blood stem cell collection containing at least 2 × 10^6 CD34+ cells/kg based on patient body weight.

  • Adequate organ function as measured by:

    • Cardiac function: Left ventricular ejection fraction at rest ≥40%
    • Hepatic function: Bilirubin ≤2 × ULN and aspartate amino transferase/alanine amino transferase (AST/ALT) ≤3 × ULN
    • Renal function: Creatinine clearance ≥40 mL/minute (measured or calculated/estimated)
    • Pulmonary function: Carbon monoxide diffusing capacity (DLCO; corrected for hemoglobin [Hgb]), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC) ≥50% of predicted value
    • Oxygen saturation ≥92% on room air
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  • Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion Criteria:

  • Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior to ASCT
  • Prior stem cell transplant (autologous or allogeneic)
  • Smoldering MM not requiring therapy
  • Plasma cell leukemia
  • Systemic amyloid light chain amyloidosis
  • Active bacterial, viral, or fungal infection
  • Seropositive for human immunodeficiency virus (HIV)
  • Known, active hepatitis A, B, or C Infection
  • Pregnant or breastfeeding.
  • Receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 7 days prior to the ASCT or planning to receive any of these treatments prior to the last study visit on Day +100.
  • Hypersensitive or intolerant to any component of the study drug(s) formulation
  • Receiving growth factors (filgrastim, XM02-filgrastim, peg-filgrastim, plerixafor, etc) or undergoing apheresis < 14 days prior to the start of treatment on protocol (Day -7).

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental: Granix and high dose melphalan (HDM)

Control: High dose melphalan (HDM)

Arm Description

Granix on Day -7 through Day -2. HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0

HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0.

Outcomes

Primary Outcome Measures

Number of Participants With Complete Response or Stringent Complete Response
Complete response (CR) requires all of the following: Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine <5% plasma cells in the bone marrow Disappearance of soft tissue plasmacytomas Stringent complete response (sCR) requires all of the following: CR as defined above Normal free light chain ratio Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence

Secondary Outcome Measures

Number of Participants With Adverse Events
-Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Number of Participants With Overall Response
Overall response rate=CR+sCR+VGPR+PR Complete response (CR), disappearance of monoclonal protein from the blood & urine and <5% plasma cells in bone marrow &disappearance of soft tissue plasmacytomas Stringent complete response (sCR), CR & normal free light chain ratio & absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence Very good partial response (VGPR), serum and urine monoclonal protein detectable by immunofixation but not on electrophoresis OR > 90% reduction in serum monoclonal protein with urine monoclonal protein < 100 mg per 24 hours and if present, > 50% reduction in the size of soft tissue plasmacytomas Partial response (PR), > 50% reduction in the level of the serum monoclonal protein & reduction in urine monoclonal protein & > 50% reduction in the size of soft tissue plasmacytomas & if serum and urine monoclonal protein are unmeasurable and serum free light chain is unmeasurable, a > 50% reduction in plasma cells is required
Overall Survival as Measured by Number of Participants Alive at Last Follow-up
OS is defined as the duration from the time of transplant Day 0 to death or last follow-up.
Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up
PFS is defined as the duration from time of transplant Day 0 to time of first progression/clinical relapse, death, or the date the patient was last known to be in remission
Number of Participants With Neutrophil Engraftment
Neutrophil engraftment is defined as ANC ≥ 0.5 × 10^9/L × 3 consecutive daily assessments. The first of 3 consecutive days for which ANC ≥ 0.5 × 109/L will be recorded as the date of neutrophil engraftment. Time to neutrophil engraftment will be calculated as the time from the date of the ASCT to the date of neutrophil engraftment.
Number of Participants With Platelet Engraftment
Platelet engraftment is defined as an untransfused platelet measurement >20,000/mm3 × 3 consecutive daily assessments. The first of 3 consecutive days for which the untransfused platelet measurement is >20,000/mm3 will be recorded as the date of platelet engraftment. Time to platelet engraftment will be calculated as the time from receiving the date of ASCT to the date of platelet engraftment. Untransfused is defined as no transfusions within 7 days.

Full Information

First Posted
April 4, 2014
Last Updated
November 15, 2019
Sponsor
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT02112045
Brief Title
A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Transplantation
Official Title
A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to results of interim analysis
Study Start Date
January 20, 2015 (Actual)
Primary Completion Date
December 13, 2017 (Actual)
Study Completion Date
September 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial compares how well adding XMO2 Filgrastim (Granix) to melphalan before a stem cell transplant works in treating patients with multiple myeloma. Chemotherapy drugs, such as melphalan, are given to prepare the bone marrow for the stem cell transplant. Giving colony-stimulating factors, such as XMO2 Filgrastim (Granix), may help multiple myeloma cells move from the patient's bone marrow to the blood where they may be more sensitive to treatment with melphalan. It is not yet known whether adding XMO2 Filgrastim (Granix) to melphalan before a stem cell transplant will work better than melphalan alone in treating multiple myeloma

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Granix and high dose melphalan (HDM)
Arm Type
Experimental
Arm Description
Granix on Day -7 through Day -2. HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0
Arm Title
Control: High dose melphalan (HDM)
Arm Type
Active Comparator
Arm Description
HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0.
Intervention Type
Drug
Intervention Name(s)
Granix
Other Intervention Name(s)
XM02 filgrastim
Intervention Type
Drug
Intervention Name(s)
High dose melphalan (HDR)
Other Intervention Name(s)
Alkeran® Tablets, Phenylalanine mustard
Intervention Type
Procedure
Intervention Name(s)
Autologous Stem Cell Transplant (ASCT)
Primary Outcome Measure Information:
Title
Number of Participants With Complete Response or Stringent Complete Response
Description
Complete response (CR) requires all of the following: Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine <5% plasma cells in the bone marrow Disappearance of soft tissue plasmacytomas Stringent complete response (sCR) requires all of the following: CR as defined above Normal free light chain ratio Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
Time Frame
Day +100
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
-Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame
Up through Day 30
Title
Number of Participants With Overall Response
Description
Overall response rate=CR+sCR+VGPR+PR Complete response (CR), disappearance of monoclonal protein from the blood & urine and <5% plasma cells in bone marrow &disappearance of soft tissue plasmacytomas Stringent complete response (sCR), CR & normal free light chain ratio & absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence Very good partial response (VGPR), serum and urine monoclonal protein detectable by immunofixation but not on electrophoresis OR > 90% reduction in serum monoclonal protein with urine monoclonal protein < 100 mg per 24 hours and if present, > 50% reduction in the size of soft tissue plasmacytomas Partial response (PR), > 50% reduction in the level of the serum monoclonal protein & reduction in urine monoclonal protein & > 50% reduction in the size of soft tissue plasmacytomas & if serum and urine monoclonal protein are unmeasurable and serum free light chain is unmeasurable, a > 50% reduction in plasma cells is required
Time Frame
Up to 2 years
Title
Overall Survival as Measured by Number of Participants Alive at Last Follow-up
Description
OS is defined as the duration from the time of transplant Day 0 to death or last follow-up.
Time Frame
Up to 2 years
Title
Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up
Description
PFS is defined as the duration from time of transplant Day 0 to time of first progression/clinical relapse, death, or the date the patient was last known to be in remission
Time Frame
Up to 2 years
Title
Number of Participants With Neutrophil Engraftment
Description
Neutrophil engraftment is defined as ANC ≥ 0.5 × 10^9/L × 3 consecutive daily assessments. The first of 3 consecutive days for which ANC ≥ 0.5 × 109/L will be recorded as the date of neutrophil engraftment. Time to neutrophil engraftment will be calculated as the time from the date of the ASCT to the date of neutrophil engraftment.
Time Frame
Up to Day 30
Title
Number of Participants With Platelet Engraftment
Description
Platelet engraftment is defined as an untransfused platelet measurement >20,000/mm3 × 3 consecutive daily assessments. The first of 3 consecutive days for which the untransfused platelet measurement is >20,000/mm3 will be recorded as the date of platelet engraftment. Time to platelet engraftment will be calculated as the time from receiving the date of ASCT to the date of platelet engraftment. Untransfused is defined as no transfusions within 7 days.
Time Frame
Up to Day 100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Symptomatic multiple myeloma requiring treatment Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy At least 18 years of age Adequate autologous stem cell collection, defined as an unmanipulated, cryopreserved, peripheral blood stem cell collection containing at least 2 × 10^6 CD34+ cells/kg based on patient body weight. Adequate organ function as measured by: Cardiac function: Left ventricular ejection fraction at rest ≥40% Hepatic function: Bilirubin ≤2 × ULN and aspartate amino transferase/alanine amino transferase (AST/ALT) ≤3 × ULN Renal function: Creatinine clearance ≥40 mL/minute (measured or calculated/estimated) Pulmonary function: Carbon monoxide diffusing capacity (DLCO; corrected for hemoglobin [Hgb]), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC) ≥50% of predicted value Oxygen saturation ≥92% on room air Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Able to understand and willing to sign an IRB-approved written informed consent document Exclusion Criteria: Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior to ASCT Prior stem cell transplant (autologous or allogeneic) Smoldering MM not requiring therapy Plasma cell leukemia Systemic amyloid light chain amyloidosis Active bacterial, viral, or fungal infection Seropositive for human immunodeficiency virus (HIV) Known, active hepatitis A, B, or C Infection Pregnant or breastfeeding. Receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 7 days prior to the ASCT or planning to receive any of these treatments prior to the last study visit on Day +100. Hypersensitive or intolerant to any component of the study drug(s) formulation Receiving growth factors (filgrastim, XM02-filgrastim, peg-filgrastim, plerixafor, etc) or undergoing apheresis < 14 days prior to the start of treatment on protocol (Day -7).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meagan Jacoby, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Transplantation

We'll reach out to this number within 24 hrs